ArticleMolecular psychiatry2024
A naturally occurring variant of SHLP2 is a protective factor in Parkinson's disease.
Article in Molecular psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 15 citations in OpenAlex.
- A peripheral perspective on brain health: vascular and skeletal muscle contributions.American journal of physiology. Heart and circulatory physiology · 2026Review
- An immune-associated mitochondrial DNA variant with sex differences reveals a putative novel microprotein called MASL.Immunity & ageing : I & A · 2026Article
- Mitochondrial bioenergetic signatures differentiate asymptomatic from symptomatic Alzheimer's disease.Communications biology · 2026Article
- Small but mighty: mitochondrial DNA at the centre of retrograde signalling.Cell communication and signaling : CCS · 2026Review
- Mitochondrial-derived microproteins in lung disease: insights and implications.American journal of physiology. Lung cellular and molecular physiology · 2026Review
- Mitochondria-derived peptides in liver disease: Emerging regulators of hepatic metabolism and therapeutic targets.Hepatology communications · 2026Review
- MENTSH: A novel mitochondrial microprotein linked to a SNP associated with type 2 diabetes.Theranostics · 2026Article
- Age-diet interactions significantly influence intratumoral gene expression, gut microbiome signature and tumor microenvironment in colorectal cancer.Neoplasia (New York, N.Y.) · 2025Article
- Mitochondrial-Derived Peptides: Implication in the Therapy of Neurodegenerative Diseases.Molecular neurobiology · 2025Review
- Mitochondrial bioenergetic signatures differentiate asymptomatic from symptomatic Alzheimer's disease.bioRxiv : the preprint server for biology · 2025Article
- Mitochondrial Microproteins: Emerging Regulators in Neurodevelopment and Neurodegeneration.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Mitochondrial-derived microproteins: from discovery to function.Trends in genetics : TIG · 2025Review
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Mechanism and Clinical Application Prospects of Mitochondrial DNA Single Nucleotide Polymorphism in Neurodegenerative Diseases.Neurochemical research · 2024Review
- Parkinson's Disease: Biomarkers for Diagnosis and Disease Progression.International journal of molecular sciences · 2024Review
- Investigating the Protective Role of the Mitochondrial 2158 T > C Variant in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2024Article
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Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
Abstract
Mitochondrial DNA single nucleotide polymorphisms (mtSNPs) have been associated with a reduced risk of developing Parkinson's disease (PD), yet the underlying mechanisms remain elusive. In this study, we investigate the functional role of a PD-associated mtSNP that impacts the mitochondrial-derived peptide (MDP) Small Humanin-like Peptide 2 (SHLP2). We identify m.2158 T > C, a mtSNP associated with reduced PD risk, within the small open reading frame encoding SHLP2. This mtSNP results in an alternative form of SHLP2 (lysine 4 replaced with arginine; K4R). Using targeted mass spectrometry, we detect specific tryptic fragments of SHLP2 in neuronal cells and demonstrate its binding to mitochondrial complex 1. Notably, we observe that the K4R variant, associated with reduced PD risk, exhibits increased stability compared to WT SHLP2. Additionally, both WT and K4R SHLP2 show enhanced protection against mitochondrial dysfunction in in vitro experiments and confer protection against a PD-inducing toxin, a mitochondrial complex 1 inhibitor, in a mouse model. This study sheds light on the functional consequences of the m.2158 T > C mtSNP on SHLP2 and provides insights into the potential mechanisms by which this mtSNP may reduce the risk of PD.
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